Gene correction therapies: getting there
Unprecedented technological progress now enables precise correction of DNA-mutations. The main roadblock to use these technologies to treat patients with genetic diseases, is getting the gene correctors in the affected organs of the patient. Supported by the pharmaceutical company Takeda, we aim to study and develop innovative delivery strategies for gene-correction in specific organ cells.
Rare genetic diseases affect >30 million people in Europe. Development of therapies is hampered by the low prevalence and high heterogeneity of individual diseases. However, all these diseases have the same root cause: genetic mutations. Gene-correction therapies would revolutionize prospects for this large group of patients with generally severe and untreatable diseases.
In this project, we will develop FluoCODE: a mouse model with a fluorescent green gene in all cells. Using the newest gene editors, this green fluorescence can be turned into blue. We will optimize the gene-editors and test and adapt innovative (lipid-based, virus-like and viral) delivery vectors and quantify blue and green fluorescence in the different organ cells of fluoCODE-mice. Evolving insights will guide further development of delivery systems to the liver, a relatively easy-to-reach organ, enabling cell-specific delivery analysis. With Takeda’s liver expertise, we will develop and test a gene-correction and delivery strategy for a rare genetic liver disease: progressive familial intrahepatic cholestasis (PFIC) in patient-derived liver cells and PFIC-mice. In addition to laying the basis to develop gene-correction therapies in the liver, we will use resulting insights to develop systems to target the different cell-types of the difficult-to-reach-but-so-desirable brain.
With this project, we will develop the fluoCODE-platform to study and develop gene therapies focusing on the liver and brain, but applicable to any organ or cell-type. This will accelerate clinical translation of gene therapies for the many patients with genetic disease.
